Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial

J Clin Psychiatry. 2015 Aug;76(8):1075-84. doi: 10.4088/JCP.14m09123.

Abstract

Objective: Obsessive-compulsive disorder (OCD) affects approximately 2.5% of the population and is associated with significant morbidity. Many patients receive little benefit from the best available treatments, and even those who do respond often suffer from significant residual symptoms. Convergent evidence suggests that abnormalities in glutamate homeostasis and neurotransmission may contribute to OCD and that glutamate-modulating medications may be of benefit in patients whose symptoms are refractory to standard interventions. Small open-label trials of augmentation of serotonin reuptake inhibitor (SRI) pharmacotherapy with the glutamate modulator riluzole have suggested benefit in adults with refractory symptoms. We report a pilot randomized placebo-controlled trial of riluzole augmentation of ongoing SRI treatment in SRI-refractory patients.

Method: Outpatients (n = 27) and inpatients (n = 11) with DSM-IV OCD on stable SRI pharmacotherapy were randomized between November 2006 and December 2012 to receive riluzole 50 mg or placebo twice a day and followed for 12 weeks after a 2-week placebo lead-in phase.

Results: Riluzole was well tolerated; 1 patient experienced moderate nausea, but none discontinued treatment due to side effects. While there was nominally greater Y-BOCS improvement in the riluzole group (our primary outcome) compared to placebo, it did not reach statistical significance. In the outpatient subsample, a trend suggesting benefit from riluzole augmentation for obsessions (P = .056, 2-tailed, uncorrected) was found in a secondary analysis. Among outpatients, more achieved at least a partial response (> 25% improvement) with riluzole than with placebo (P = .02 in a secondary analysis).

Conclusions: Riluzole may be of benefit to a subset of patients. Larger samples would be required to detect effects of the order suggested by the nominal improvement in our outpatient subsample.

Trial registration: ClinicalTrials.gov identifier: NCT00523718.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Synergism
  • Drug Therapy, Combination
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Pilot Projects
  • Riluzole / administration & dosage
  • Riluzole / adverse effects
  • Riluzole / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Excitatory Amino Acid Antagonists
  • Serotonin Uptake Inhibitors
  • Riluzole

Associated data

  • ClinicalTrials.gov/NCT00523718